Neutral sphingomyelinase is a magnesium sensitive enzyme that is a member of the sphingomyelinase family, that catalyzes the hydrolytic cleavage of sphingomyelin to ceramide and phosphocholine at neutral pH optima. Ceramide and phosphocholine have a role as lipid second messengers in multiple signal transduction pathways including pathways involved in cell proliferation, apoptosis, and differentiation. Neutral sphingomyelinase may be involved in a wide variety of human diseases and conditions, including insulin resistant diabetes, arthritis, inflammation, cancer, and atherosclerosis. A review of the properties of Neutral sphingomyelinase is found in Chatterjee, S., Chemistry and Physics of Lipids, 102 (1999) pp79-96.
This invention relates to a series of small molecules that bind to neutral sphingomyelinase and inhibit the enzyme's activity. The invention includes pharmaceutical compositions containing these compounds, their methods of production as well as intermediates used in their synthesis. The present invention also includes methods of treating a patient suffering from a disorder that is related to the activity of neutral sphingomyelinase.